Key result
Extended viral polymerase primer grip enhances RNA recombination and prevents ribavirin-induced error catastrophe in poliovirus.
Why the study?
It was unknown whether viruses can distinguish between homologous and nonhomologous partners during sexual RNA replication.
Identifies the structural basis in the viral polymerase responsible for sexual RNA replication, highlighting a mechanism by which picornaviruses evade error catastrophe.
Answers are grounded in this paper and cite their sources.
May inform picornavirus antiviral design targeting polymerase fidelity; leaves open translation to human therapies.
Picornaviruses have both asexual and sexual RNA replication mechanisms. Sexual RNA replication shapes picornavirus species groups, contributes to the emergence of vaccine-derived polioviruses, and counteracts error catastrophe. Can viruses distinguish between homologous and nonhomologous partners during sexual RNA replication? We implicate an extended primer grip of the viral polymerase in sexual RNA replication mechanisms. By sensing RNA sequence complementarity near the active site, the extended primer grip of the polymerase has the potential to distinguish between homologous and nonhomologous RNA templates during sexual RNA replication.
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Kempf et al. (2020) studied Picornavirus infection. Serial passage in ribavirin / Polymerase mutagenesis vs. Wildtype poliovirus / 0 uM ribavirin was evaluated on Viral RNA recombination frequency and ribavirin resistance. An extended primer grip of the viral polymerase facilitates efficient sexual RNA replication and counteracts ribavirin-induced error catastrophe in polioviruses.
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